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AR045955A1 - BENZOIMIDAZOLIC COMPOUNDS - Google Patents

BENZOIMIDAZOLIC COMPOUNDS

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Publication number
AR045955A1
AR045955A1 ARP040103534A ARP040103534A AR045955A1 AR 045955 A1 AR045955 A1 AR 045955A1 AR P040103534 A ARP040103534 A AR P040103534A AR P040103534 A ARP040103534 A AR P040103534A AR 045955 A1 AR045955 A1 AR 045955A1
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AR
Argentina
Prior art keywords
alkyl
independently
cyclic structure
alkoxy
assignments
Prior art date
Application number
ARP040103534A
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Spanish (es)
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Janssen Pharmaceutica Nv
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Publication of AR045955A1 publication Critical patent/AR045955A1/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/18Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • CCHEMISTRY; METALLURGY
    • C04CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04BLIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B35/00Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
    • C04B35/622Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
    • C04B35/626Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
    • C04B35/63Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
    • C04B35/632Organic additives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • C07K2317/53Hinge
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2318/00Antibody mimetics or scaffolds
    • C07K2318/10Immunoglobulin or domain(s) thereof as scaffolds for inserted non-Ig peptide sequences, e.g. for vaccination purposes

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Manufacturing & Machinery (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Ceramic Engineering (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Inorganic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Materials Engineering (AREA)
  • Structural Engineering (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Compuestos benzoimidazólicos, composiciones y métodos para usarlos en la inhibición del reclutamiento de leucocitos, en la modulación del receptor H4 y en el tratamiento de afecciones tales como inflamación, afecciones mediadas por el receptor H4 y afecciones relacionadas. Reivindicación 1: Un compuesto de fórmula (1) o (2), en las cuales: W es N o CR7; X es N o CH; Y es O, NR12 o CR12R13; Z es N o CR14; n es 0, 1 ó 2; cada uno de R1-4 es, independientemente de otras asignaciones de sustituyentes, H, alquilo C1-4, alquenilo C2-5, alquinilo C2-5, cicloalquilo C3-6, alcoxi C1-4, alquilamino C1-4, alquiltio C1-4, alquilsulfonilo C1-4, -Ocicloalquilo C3-6, -OCH2Ph, ciano, CF3, F, Cl, Br, I, nitro, -OCF3, -SCF3, -ORC, -SRC, -S(O)RC, -SO2RC, -C(O)RC, fenilo, bencilo, fenetilo, -C(O)NRaRb, -C(O)ORc, -NRaRb, -CH2NRaRb o -CH2ORc; donde cada uno de Ra, Rb y Rc se selecciona, independientemente de otras asignaciones de sustituyentes, de H, alquilo C1-4, cicloalquilo C3-6, fenilo, (cicloalquil-C3-6)alquilo C1-2, bencilo y fenetilo, o Ra y Rb tomados junto con el nitrógeno al cual se encuentran unidos, forman un anillo heterocíclico de 4-7 miembros HetCyc1, donde dicho anillo HetCyc1 posee 0 ó 1 heteroátomos adicionales seleccionados de O, S, >NH y >Nalquilo C1-6 y donde cualquier resto fenilo, fenetilo, bencilo, alquilo o cicloalquilo en cualquiera de dichos R1-4, Ra, Rb, Rc y dicho anillo HetCyc1 está sustituido opcionalmente, e independientemente de otras asignaciones de sustituyentes, con 1, 2 ó 3 sustituyentes seleccionados de alquilo C1-3, halo, hidroxi, amino y alcoxi C1-3; cada uno de R5-7 es, independientemente de otras asignaciones de sustituyentes, H, alquilo C1-6, F, Cl, Br, I, CF3, -OCF3, - ORC, -SRC, -S(O)RC, -SO2RC, alcoxi C1-4, ciano, nitro, -C(O)NRaRb, -C(O)fenilo, -C(O)-alquilo C1-6, -S(O)-alquilo C1-4 o -SO2-alquilo C1-4; o, R5 y R6 para un compuesto de fórmula (1) tomados junto con los átomos de carbono a los que están unidos forman una estructura cíclica Cyc1 seleccionada de arilo, heteroarilo, carbociclo de 5 ó 6 miembros y heterociclo de 5 ó 6 miembros con 1 ó 2 heteroátomos, donde dicha estructura cíclica Cyc1 está sustituida, independientemente de otras asignaciones de sustituyentes, con 0, 1 ó 2 sustituyentes seleccionados de alquilo C1-3, halo, hidroxi, amino y alcoxi C1-3; o R7 y R6 para un compuesto de fórmula (2) tomados junto con los átomos de carbono a los que están unidos forman una estructura cíclica Cyc2 seleccionada de arilo, heteroarilo, carbociclo de 5 ó 6 miembros y heterociclo de 5 ó 6 miembros con 1 ó 2 heteroátomos, donde dicha estructura cíclica Cyc2 está sustituida, independientemente de otras asignaciones de sustituyentes, con 0, 1 ó 2 sustituyentes seleccionados de alquilo C1-3, halo, hidroxi, amino y alcoxi C1-3; R8 es, independientemente de otras asignaciones de sustituyentes, H o alquilo C1-6, o R9 y R10 tomados juntos forman una estructura cíclica de 5-6 miembros Cyc3, donde dicha estructura cíclica Cyc3 es un carbociclo de 5 ó 6 miembros o un heterociclo de 5 ó 6 miembros con 1 ó 2 heteroátomos y donde dicha estructura cíclica Cyc3 está sustituida, independientemente de otras asignaciones de sustituyentes, con 0, 1 ó 2 sustituyentes seleccionados de alquilo C1-3, halo, hidroxi, amino y alcoxi C1-3; R11 es H o alquilo C1-4; cada uno de R12 y R13 es, independientemente de otras asignaciones de sustituyentes, H, o alquilo C1-4; o, cuando Y es CR12R13, R12 y R13 tomados junto con el miembro de carbono al cual se encuentran unidos forman una estructura cíclica Cyc4 sustituida opcionalmente, donde dicha estructura cíclica Cyc4 es un carbociclo de 3 a 6 miembros o un heterociclo de 3 a 6 miembros con 0 o 1 heteroátomos adicionales, o CR12R13 es C=O; R14 es, H, alquilo C1-4, OH o alcoxi C1-4; un enantiómero, diastereómero, racemato del mismo, o una sal, amida o éster aceptable para uso farmacéutico del mismo; siempre que: cuando Y es O ó NR12, entonces Z sea CR14 y R8 no sea OH o alcoxi C1-4; cuando Z es N, Y sea CR12R13; y ninguno de R1 o R4 sea C(O)NH2.Benzoimidazole compounds, compositions and methods for use in the inhibition of leukocyte recruitment, in the modulation of the H4 receptor and in the treatment of conditions such as inflammation, conditions mediated by the H4 receptor and related conditions. Claim 1: A compound of formula (1) or (2), in which: W is N or CR7; X is N or CH; Y is O, NR12 or CR12R13; Z is N or CR14; n is 0, 1 or 2; each of R1-4 is, independently of other substituent assignments, H, C1-4 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 alkylamino, C1- alkylthio 4, C 1-4 alkylsulfonyl, -C3-6 cycloalkyl, -OCH2Ph, cyano, CF3, F, Cl, Br, I, nitro, -OCF3, -SCF3, -ORC, -SRC, -S (O) RC, - SO2RC, -C (O) RC, phenyl, benzyl, phenethyl, -C (O) NRaRb, -C (O) ORc, -NRaRb, -CH2NRaRb or -CH2ORc; where each of Ra, Rb and Rc is independently selected from other assignments of substituents, H, C1-4 alkyl, C3-6 cycloalkyl, phenyl, (C3-6 cycloalkyl) C1-2 alkyl, benzyl and phenethyl, or Ra and Rb taken together with the nitrogen to which they are attached, form a 4-7 membered HetCyc1 heterocyclic ring, wherein said HetCyc1 ring has 0 or 1 additional heteroatoms selected from O, S,> NH and> C1-6 Nalkyl and wherein any phenyl, phenethyl, benzyl, alkyl or cycloalkyl moiety in any of said R1-4, Ra, Rb, Rc and said HetCyc1 ring is optionally substituted, and independently of other substituent assignments, with 1, 2 or 3 substituents selected C1-3 alkyl, halo, hydroxy, amino and C1-3 alkoxy; each of R5-7 is, independently of other substituent assignments, H, C1-6 alkyl, F, Cl, Br, I, CF3, -OCF3, - ORC, -SRC, -S (O) RC, -SO2RC , C1-4 alkoxy, cyano, nitro, -C (O) NRaRb, -C (O) phenyl, -C (O) -C1-6 alkyl, -S (O) -C 1-4 alkyl or -SO2-alkyl C1-4; or, R5 and R6 for a compound of formula (1) taken together with the carbon atoms to which they are attached form a Cyc1 cyclic structure selected from aryl, heteroaryl, 5 or 6 membered carbocycle and 5 or 6 member heterocycle with 1 or 2 heteroatoms, wherein said Cyc1 cyclic structure is substituted, independently of other assignments of substituents, with 0, 1 or 2 substituents selected from C1-3 alkyl, halo, hydroxy, amino and C1-3 alkoxy; or R7 and R6 for a compound of formula (2) taken together with the carbon atoms to which they are attached form a Cyc2 cyclic structure selected from aryl, heteroaryl, 5 or 6 membered carbocycle and 5 or 6 member heterocycle with 1 or 2 heteroatoms, wherein said Cyc2 cyclic structure is substituted, independently of other assignments of substituents, with 0, 1 or 2 substituents selected from C1-3 alkyl, halo, hydroxy, amino and C1-3 alkoxy; R8 is, independently of other substituent assignments, H or C1-6 alkyl, or R9 and R10 taken together form a 5-6 Cyc3 cyclic structure, wherein said Cyc3 cyclic structure is a 5 or 6 membered carbocycle or a heterocycle 5 or 6 members with 1 or 2 heteroatoms and wherein said Cyc3 cyclic structure is substituted, independently of other assignments of substituents, with 0, 1 or 2 substituents selected from C1-3 alkyl, halo, hydroxy, amino and C1-3 alkoxy ; R11 is H or C1-4 alkyl; each of R12 and R13 is, independently of other assignments of substituents, H, or C1-4 alkyl; or, when Y is CR12R13, R12 and R13 taken together with the carbon member to which they are attached form an optionally substituted Cyc4 cyclic structure, wherein said Cyc4 cyclic structure is a 3 to 6 member carbocycle or a 3 to 6 heterocycle members with 0 or 1 additional heteroatoms, or CR12R13 is C = O; R14 is, H, C1-4 alkyl, OH or C1-4 alkoxy; an enantiomer, diastereomer, racemate thereof, or a salt, amide or ester acceptable for pharmaceutical use thereof; provided that: when Y is O or NR12, then Z is CR14 and R8 is not OH or C1-4 alkoxy; when Z is N, Y is CR12R13; and none of R1 or R4 is C (O) NH2.

ARP040103534A 2003-09-30 2004-09-29 BENZOIMIDAZOLIC COMPOUNDS AR045955A1 (en)

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AR045955A1 true AR045955A1 (en) 2005-11-16

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US (10) US7432378B2 (en)
EP (1) EP1673348B1 (en)
JP (1) JP2007508011A (en)
KR (1) KR20060097024A (en)
CN (1) CN1886380B (en)
AR (1) AR045955A1 (en)
AT (1) ATE427303T1 (en)
AU (1) AU2004286933B2 (en)
BR (1) BRPI0414918A (en)
CA (1) CA2540704A1 (en)
DE (1) DE602004020364D1 (en)
ES (1) ES2323178T3 (en)
HR (1) HRP20060126A2 (en)
IL (1) IL174677A0 (en)
NO (1) NO20061950L (en)
NZ (1) NZ546259A (en)
PT (1) PT1673348E (en)
RU (1) RU2006110561A (en)
TW (1) TW200526637A (en)
WO (1) WO2005044807A2 (en)
ZA (1) ZA200603411B (en)

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ZA200603411B (en) 2007-07-25
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US7662966B2 (en) 2010-02-16
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